The goal of this project is to demonstrate in a large, randomized clinical trial the efficacy of one or more pharmacologic interventions in measurably slowing the progession of Parkinson's disease. The major source of motor disability in PD is the loss of dopamine cells in the midbrain substantia nigra. Current symptomatic treatments improve motor function, but do not slow the advance of the disease over time. A neuroprotective therapy is a treatment which protects or rescues nigral dopamine cells, and retards the progression of the disease. After a series of pilot studies of candidate therapies, the clinical centers will embark on a large clinical trial involving an estimated 3000 patients with early PD, followed for five years. The end point will be defined in terms of clinical measures of disease progression. We are applying to be a clinical center for this project. A detailed protocol will be drafted by the Steering Committee, membership of which will include representatives of the clinical centers. A plan is presented for the accrual and retention of patients with early Parkinson's disease at this site. Parkinson's disease is a common neurodegerative disease, affecting more than a million Americans. It is a major source of disability and lost productivity. A treatment which slows disease progression by 50% would take the disability which accumulates over 15-20 years, and extend it out over 30-40 years, improving function and quality of life at each point along the way.